EARLY VERSUS LATE SURFACTANT TREATMENT IN PRETERM INFANTS OF 27 TO 32WEEKS GESTATIONAL-AGE - A MULTICENTER CONTROLLED CLINICAL-TRIAL

Objective. To investigate whether early (<1 hour after birth) surfacta nt administration would be superior to late treatment (2-6 hours after birth) in preterm infants. Study Design. Randomized controlled multic enter clinical trial. Patients and Methods. Prenatal randomization of all infants of 27 to 32 weeks' gestational age stratified by center af ter parental informed consent. Early treatment: 100 mg/kg body weight bovine surfactant (SF-RI1, Alveo-fact; Dr K. Thomae, Biberach, Germany ) to infants requiring intubation after birth. Late treatment: identic al dosage to infants requiring intubation up to 6 hours of age with th e fraction of inspired oxygen >0.4 at 2 to 6 hours after birth. Primar y endpoint: the time on mechanical ventilation. Main secondary endpoin ts: mortality, bronchopulmonary dysplasia, intraventricular hemorrhage greater than or equal to grade III, and periventricular leukomalacia. Sample site calculation: at least 280 infants to prove superiority of either approach (alpha = 0.05; beta = 0.90). Results. Enrollment of 3 17 infants, 154 randomized to early surfactant treatment, 163 to late surfactant treatment. Study infants (all following data intent-to-trea t groups: early versus late surfactant) were similar with respect to: gestational age, 29.5 +/- 1.6 weeks versus 29.7 +/- 1.6 weeks; birth w eight, 1227 +/- 367 g versus 1269 +/- 334 g; and the rate of prenatal corticosteroids, 79.9% versus 72.8%. Duration of mechanical ventilatio n: 3 days (0-8) versus 2 days (0-6) (median, interquartile); further o utcome variables: death or bronchopulmonary dysplasia (day 28) 25.9% v ersus 23.9%, mortality 3.2% versus 1.8%, intraventricular hemorrhage g reater than or equal to grade III 6.5% versus 3.7%, and periventricula r leukomalacia 5.2% versus 5.5% not differing statistically. Conclusio n. In preterm infants with a high rate of prenatal glucocorticoids, ea rly surfactant administration was not found to be superior to late tre atment in terms of relevant outcome variables.